Advanced Solid Tumor
Conditions
Brief summary
This study will evaluate the safety and tolerability of APL-102 Capsule and characterize the pharmacokinetic (PK) profile in advanced solid tumor patients.
Detailed description
This study is an open, multicenter dose-escalation study to evaluate the safety and tolerance of APL-102 and obtain the relevant data of APL-102 in patients with advanced solid tumors. In the dose escalation stage, based on the incidence of dose limited toxicity (DLT) and adverse event (AE), explore and determine the maximum tolerated dose (MTD) and phase II recommended dose (RP2D). After RP2D and administration protocol are determined, an extended study will be conducted on 6-10 subjects to further evaluate the safety and antitumor activity of APL-102.
Interventions
DRUGAPL-102 Capsules
Dose escalation: A total of seven dose levels (1mg, 2mg, 3mg, 5mg, 7mg, 9mg and 11mg) are planned. Dose extension: After RP2D determined, the RP2D dose level will be extended to enroll 6-10 subjects to further evaluated the safety and antitumor activity of APL-102.
Sponsors
Zhejiang CrownMab Biotech Co. Ltd
Apollomics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will be assigned to a dose level of APL-102 in the order of study entry. A total of seven therapeutic dose levels (1mg, 2mg, 3mg, 5mg, 7mg, 9mg and 11mg) are planned. To reduce the number of subjects exposed to potentially ineffective doses and protect the rights and interests of subjects, rapid titration was used in the low-dose group (1 mg, 2 mg, 3 mg); When approaching the expected effective dose of 5 mg, the 3 + 3 study design was used.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: 1. Male or female, age ≥ 18 and ≤ 75 years old. 2. Patients with unresectable or metastatic advanced solid tumors confirmed by histology or cytology, and after the failure of standard treatment, or cannot tolerate standard treatment, or have no standard treatment. 3. There were measurable lesions according to the efficacy evaluation criteria of solid tumors (RECIST version 1.1). 4. Eastern Cooperative Oncology Group(ECOG) performance status score is 0 to 1. 5. Life expectancy is more than 3 months after the first administration. 6. The organ function level must meet the following requirements: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.0× upper limit of normal value (ULN) (patients with liver metastasis≤ 5 × ULN). Serum bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3×ULN in patients with Gilbert syndrome). Absolute neutrophil count ≥ 1.5×10\^9/L. Platelet count ≥ 100×10\^9/ L. Hemoglobin ≥ 9 g / dL. 7. No other chemotherapy was received within four weeks before the first administration of the trial; All previous anti-tumor treatments, including targeted therapy and endocrine therapy, shall pass through at least five half-lives (or no more than 28 days) after receiving targeted therapy/endocrine therapy, and patient shall recover to the standard level specified in the test from the toxic reaction of the treatment. 8. For patients who have received radiotherapy for spine and/or peripheral limbs, they can only be enrolled after four weeks and two weeks before the first administration and should recover from the toxic reaction of treatment to the standard level specified in the study. 9. No major surgery was performed within four weeks before the first administration of APL-102., etc. Major
Exclusion criteria
1. In addition to the malignancies in the study, patients with systemic diseases leading to poor medical risk (such as uncontrollable infection in the active phase). 2. Life-threatening diseases, severe organ dysfunction, interference with the absorption or metabolism of APL-102, or other reasons that the researchers believe may endanger the safety of subjects or affect the integrity of research results. 3. Patients with a history of heart disease or potential risk of heart disease. 4. Patients with low circulatory function as defined by the New York Heart Association's (NYHA) functional criteria. 5. Patients with a definite diagnosis of chronic obstructive pulmonary disease, bronchial asthma or interstitial lung disease, or patients with forced expiratory volume in one second/ forced vital capacity (FEV1/FVC) ratio \< 70% in pulmonary function test. 6. Patients with decompensated cirrhosis or history of allogeneic bone marrow transplantation or organ transplantation. 7. Patients in repeated resting states during screening had mean systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or positive proteinuria (allowing antihypertensive agents to control blood pressure). 8. Have a history of human immunodeficiency virus (HIV) infection or HIV antibody positive; or seropositive results consistent with active infection for hepatitis B virus (in case of only hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive, the examination of Hepatitis B (HBV) DNA copy number is needed: HBV DNA copy number must not exceed 1,000 copies/mL or 200 IU/mL.) or hepatitis C virus. 9. Patients with the symptomatic primary brain tumor and/or secondary brain metastasis, uncontrollable antiepileptic drugs and requiring high-dose steroid treatment. Or cerebrovascular accident, transient ischemic attack, or intermittent claudication within six months before treatment. 10. Pregnant or lactating patients., etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | 36 days | Dose limiting toxicities |
| Adverse Events (AEs) | From time of informed consent signature to 30 days after the subject's last visit (approximately 1 year) | Adverse events occurred in all subjects during the study treatment according to the National Cancer Institute Common Terminology Standard for adverse events (NCI CTCAE) standard version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response(DOR) | Approximately 1 year | The duration of response in patients of advanced solid tumors |
| Progression-free survival(PFS) | Approximately 1 year | The progression-free survival in patients of advanced solid tumors |
| Overall survival(OS) | Approximately 1 year | The overall survival in patients of advanced solid tumors |
| Incidence of Adverse Events | From time of informed consent signature to 30 days after the subject's last visit (approximately 1 year) | The incidence of all adverse events with different severity (NCI CTCAE 5.0) |
| Time to reach Cmax (Tmax) | 36 days | To assess the pharmacokinetic profile in patients with advanced solid tumors. |
| The area under the plasma concentration-time curve from time zero to the last measurable time point (AUC0-t) | 36 days | To assess the pharmacokinetic profile in patients with advanced solid tumors. |
| Peak plasma concentration (Cmax) | 36 days | To assess the pharmacokinetic profile in patients with advanced solid tumors. |
| Objective response rate(ORR) | Approximately 1 year | The objective response rate in patients of advanced solid tumors |
Countries
China
Outcome results
None listed